N-Benzyltriazolium as Both Molecular Station and Barrier in

[2]Rotaxane Molecular Machines

Eric Busseron and Fre de ric Coutrot*
Supramolecular Machines and ARchitectures Team, Institut des Biomole cules Max Mousseron (IBMM) UMR 5247
CNRSUM1-UM2Universite Montpellier 2, Place Euge ne Bataillon, case courrier 1706, F-34095 Montpellier Cedex 5, France
*S Supporting Information
ABSTRACT: A two-station [2]rotaxane, consisting of a
dibenzo-24-crown-8 macrocycle (DB24C8) that surrounds a
molecular axle containing an anilinium and a monosubstituted
pyridinium amide molecular stations, has been synthesized via
alkyneazide click chemistry. The subsequent N-benzylation
of the triazole moiety, which is located in the middle of the
threaded axle, was then envisaged. In addition to aording a
third molecular station (i.e., a triazolium station) for the
DB24C8, it was found that the benzyl moiety behaves as a
kinetic molecular barrier that prevents the DB24C8 from shuttling along the molecular encircled axle from one extremity to the
other. Depending on where the DB24C8 is initially located, the N-benzylation of the triazole allows trapping of the DB24C8 on
either the left or the right side of the thread with respect to the triazolium station. The presence of the benzyl barrier thus
aords two dierent three-station [2]rotaxane molecular machines, in which some of co-conformational states remain unbalanced
and not at the equilibrium.

INTRODUCTION
Several interlocked molecular machines based on rotaxanes and
incorporating a dibenzo-24-crown-8 (DB24C8) as a macrocycle
have been reported. Most of them have been using a positively
charged moiety as molecular station for this macrocycle.
Among them, benzylic ammonium,
1
anilinium,
2
N,N-dialkyl-
4,4-bipyridinium,
3
or 1,2-bis(pyridinium)ethane cation
4
have
been used as good template to produce [2]rotaxanes. The
interactions that take place between these template moieties
and the DB24C8 are mainly based on iondipole interactions,
hydrogen bonding, and stacking between the electron-rich
catechol ring and electron-poor pyridinium rings. In 2008, we
reported the synthesis of new molecular machines based on
anilinium and triazolium stations, using a straightforward two-
step sequence: (1) alkyneazide click chemistry and (2)
methylation of the triazole.
5
In our pH-sensitive system, the
DB24C8 resides rst around the best anilinium station, while it
shuttles around the triazolium station upon deprotonation. We
then proposed some [2]rotaxane molecular machines contain-
ing new mono- and disubstituted pyridinium amide molecular
stations.
6
Among these two new molecular stations, the
disubstituted pyridinium amide was found to be a very
interesting station, when linked to a mannose via a N-
mannosidic bond. Indeed, it was able to ip the chair
conformation of the mannopyranose by switching on or o
the reverse anomeric eect, depending on its interaction with
the DB24C8. A little bit later, we then reported some three-
station-based [2]rotaxanes molecular machines, which allowed
us to determine the following increasing anity order of the
dierent stations for the DB24C8: (1) disubstituted pyridinium
amide, (2) triazolium, (3) monosubstituted pyridinium amide,
and (4) anilinium.
7
At acidic pH, we unambiguously reported
for all of our molecular machines that the DB24C8 exclusively
resides around the anilinium station. However, upon
deprotonation of the anilinium, dierent bistable or oscillating
co-conformational states were obtained depending on the
stations involved. In some molecular machines, we observed
that the deprotonation at one extremity of the threaded axle
could cause a translational shuttling of the macrocycle, which
was then able to induce a rotational movement of chemical
bonds at the other extremity of the molecule, thus to entirely
ip the chair conformation of a mannopyranose. In others, the
translational shuttling of the DB24C8 induced a braking of the
rotation of a bond.
Recently, Leigh et al. have developed the concept of the
introduction of a kinetic molecular barrier in a [2]rotaxane
molecular machine, in order to make the molecular machines
be compartmentalized.
8
Herein, we propose the synthesis of
three-station [2]rotaxane molecular machines including a
monosubstituted pyridinium amide, a N-benzyltriazolium, and
an anilinium as molecular stations. The aims are either to trap
the DB24C8 around stations of weaker anity than that of
anilinium or to see how the DB24C8 can interact with stations
only on one of the two sides of the molecular axle with respect
to the triazolium station. For this purpose, the N-
benzyltriazolium moiety was chosen so that it can be used as
both a molecular station and a barrier for the macrocycle. The
Received: February 27, 2013
Published: March 25, 2013
Article
pubs.acs.org/joc
2013 American Chemical Society 4099 dx.doi.org/10.1021/jo400414f | J. Org. Chem. 2013, 78, 40994106
obtained molecular machines have then been studied by NMR
and compared to the molecular machine obtained in the N-
methyl triazolium series. This latter undergoes an oscillating
movement of the DB24C8 between the monosubstituted
pyridinium amide and the triazolium depending on pH (Figure
1, 1). In the rst of the two new described molecular machines,
the DB24C8 oscillates between the N-benzyltriazolium and the
monosubstituted pyridinium amide stations in a manner similar
to that in the N-methyltriazolium series, however, with the
feature that this movement is not pH-dependent (Figure 1, 2a).
The second system described consists of a pH-sensitive bistable
molecular machine, where the localization of the DB24C8 is
constrained to the right side of the axle between the anilinium
and the triazolium stations, depending on pH (Figures 1 and
2b).

RESULTS AND DISCUSSION

Synthesis of the [2]Rotaxane 3 Containing Two
Molecular Stations. The interlocked [2]rotaxane 3 was
obtained, via the end-capping strategy, using the copper(I)-
catalyzed Huisgen
9
alkyneazide 1,3-dipolar cycloaddition, also
called the CuAAC click-chemistry
10
(Scheme 1), between the
azido pyridinium mannosides 1 (1 equiv) and the terminal
anilinium alkyne 2 (1 equiv) in the presence of the DB24C8 (2
equiv) and a catalytic amount of 2,6-lutidine (0.1 equiv) and
Cu(CH
3
CN)
4
PF
6
(1 equiv).
7
The [2]rotaxane 3 was isolated in
a 75% yield after silica gel chromatographic column purication
(Scheme 1).
No [3]rotaxane was detected, demonstrating the poor
anity of the monosubstituted pyridinium amide moiety for
the DB24C8.
Synthesis of the N-Methyl and N-Benzyltriazolium
Stations and Actuation of the Molecular Machines. The
N-methylation of the triazole moiety of 3 was realized using the
iodomethane as reactant and solvent. After a counteranion
exchange using ammonium hexauorophosphate, the triazo-
lium compound 4 was obtained in a high yield. At acidic pH,
the DB24C8 resides around the best anilinium station, whereas
in the [2]rotaxane 5, an oscillation of the macrocycle between
the pyridinium amide and the triazolium stations was observed
at basic pH.
7
In order to trap the macrocycle either on the left or on the
right side of the encircled molecular axle, with respect to the
triazole moiety, two dierent sequential steps were achieved.
The rst case that we envisaged was to trap the macrocycle
Figure 1. Cartoon representation of the dierent co-conformational states adopted by the three-station [2]rotaxane molecular machines in (1) the
N-methyltriazolium series and (2) the N-benzyltriazolium series. The blue, pink, green, and orange colored shapes represent, respectively, the
monosubstituted pyridinium amide station, the N-benzyl or N-methyl triazolium stations, the anilinium station, and the aniline moiety.
Figure 2.
1
H NMR spectra (400 MHz, CD
3
CN, 298 K) of (a) the
protonated [2]rotaxane 8, (b) the protonated uncomplexed thread 8u
or 9u, (c) the protonated [2]rotaxane 9, (d) the deprotonated
[2]rotaxane 10, and (e) the deprotonated uncomplexed thread 10u.
The numbering and colorings correspond to the hydrogen assign-
ments indicated in Scheme 1.
The Journal of Organic Chemistry Article
dx.doi.org/10.1021/jo400414f | J. Org. Chem. 2013, 78, 40994106 4100
between the monosubstituted pyridinium amide and the
triazolium stations, whatever the pH, using a bulky benzyl
side group as a steric molecular barrier. Thereby, in order to
yield rotaxane 8, in which the DB24C8 is located on the left
side of the molecular axle with respect to the triazolium
molecular barrier, the carbamoylated compound 6 was rst
synthesized, before being benzylated. The carbamoylation of
the anilinium initially triggered the shuttling of the macrocycle
around the pyridinium amide station, whereas subsequent
benzylation of the triazole provided a new site of interaction for
the DB24C8. This caused an oscillating movement of the
macrocycle between the pyridinium amide station and the N-
benzyltriazolium, suggesting, as already observed for rotaxane 5,
similar anities of these two stations for the DB24C8.
Subsequent decarbamoylation and acidication aorded the
anilinium [2]rotaxane 8. Even though the anilinium is a better
binding site for the DB24C8, absolutely no change in the
oscillating movement was noticed, demonstrating the ecient
role of molecular barrier of the benzyl group, which trapped the
macrocycle on only one compartment of the axle.
In addition, we envisaged the trapping of the macrocycle on
the other side of the triazolium moiety, that is to say, between
Scheme 1. Synthetic Routes to Oscillating or Bistable Molecular Machines Containing an Anilinium, a Mono-substituted
Pyridinium Amide, and a Triazolium as Molecular Stations
The Journal of Organic Chemistry Article
dx.doi.org/10.1021/jo400414f | J. Org. Chem. 2013, 78, 40994106 4101
the anilinium and the triazolium stations. This was achieved in a
more straightforward route than before since the macrocycle
initially resides around the best anilinium molecular station.
Thus, N-benzylation of the triazole moiety, followed by
counteranion exchange, was rst carried out on the protonated
anilinium rotaxane 3 and aorded the [2]rotaxane 9 in a 79%
yield. In this protonated compound, the DB24C8 resides
around the best anilinium station. However, the deprotonation
of the anilinium station, using the Hunigs base
11
diisopropy-
lethylamine, triggers the shuttling of the DB24C8 around the
N-benzyltriazolium station (rotaxane 10). In comparison with
the oscillating [2]rotaxane 7, here no localization of the
DB24C8 around the pyridinium amide station was noticed,
demonstrating once again the ecient role of molecular barrier
of the bulky benzyl side group. Furthermore, due to the steric
hindrance of the benzyl group, dierences in the localization of
the DB24C8 around the triazolium station could be revealed by
1
H NMR spectroscopy between the [2]rotaxanes 8 and 10.
Molecular Machinery on Rotaxane in the Benzyl
Series. Oscillating Molecular Machine 8. The comparison
of
1
H NMR spectra between the protonated [2]rotaxane 8 and
the uncomplexed thread 8u reveals the interlocked molecular
architecture and the localization of the DB24C8 along the
threaded axle in 8 (Figure 2a,b). Indeed, the
1
H NMR signals
for the hydrogens H
A
H
E
belonging to the crown ether are
noticed in rotaxane 8, and among them, signals for hydrogens
H
E
are split, indicating that they are facing the two
nonsymmetrical extremities of the encircled molecular axle.
Interestingly, the hydrogens H
1718
, H
8
, and to a lesser extent
H
11
, all belonging, to the triazolium and to the pyridinium
amide stations, are more or less shifted downeld in the
[2]rotaxane 8 (respectively, = +0.24, +0.28, +0.47, and
+0.03 ppm) due to their hydrogen bonding interactions with
the oxygen atoms of the DB24C8. Moreover, in 8, the
hydrogens H
33
and H
20
, which are, respectively, either part of
the steric molecular benzyl barrier or just on the other side of it
with respect to the DB24C8, experience the shielding eect of
the aromatic ring of the DB24C8 (respectively, = 0.25 and
0.27 ppm). In a similar manner, the hydrogens of the aliphatic
chain H
1215
and to a lesser extent H
16
are all shielded (
from 0.29 to 0.07 ppm) as a result of of their localization in
the shielding cavity of the aromatic rings of the DB24C8 upon
the oscillation of the DB24C8. No other signicant variation of
chemical shift is observed for the other hydrogens of the
molecular axle and more especially for the hydrogens H
25
belonging to the anilinium station. This last observation
demonstrates the absence of any interaction between the
anilinium station and the DB24C8. This also proves the
ecient role of the benzyl group, which prevents the DB24C8
from shuttling until the best anilinium station. Instead, due to
the steric constraint imposed by the molecular barrier, the
macrocycle is obliged to interact with both the triazolium and
the pyridinium amide stations, which have each very similar
binding anities for the DB24C8, but much poorer than that of
anilinium. As already observed with the N-methyltriazolium 5, a
fast oscillation at the NMR time scale between these two
stations occurred. This was revealed by the presence of only
one set of NMR signals. Obviously, the deprotonation of the
anilinium in 8 caused no change in the oscillating movement of
the macrocycle because of the presence of the benzyl molecular
barrier.
pH-Sensitive Bistable Molecular Machine 9/10. The
comparison between the
1
H NMR spectra of the protonated
uncomplexed thread 9u and the [2]rotaxane 9 reveals the
presence and the localization of the DB24C8 (Figure 2b,c). As
usual, the
1
H NMR signals for the hydrogen atoms of the
crown ether H
AE
are split since they are facing the two
nonsymmetrical ends of the encircled thread. More interest-
ingly, only the chemical shift relative to the anilinium station,
i.e., hydrogen atoms H
25
, is tremendously shifted downeld in
rotaxane 9 ( = +1.02 ppm), due to their interactions by
hydrogen bonding with the oxygen atoms of the DB24C8. At
the same time, one can notice in 9 an upeld shift of the
hydrogens H
18
and H
2023
( from 0.14 to 0.44 ppm),
suggesting a shielding eect due to their localization in the
cavity of the aromatic ring of the DB24C8. No other variation
in chemical shift was noticed, which is compatible with an
evident localization of the DB24C8 around the best anilinium
station. After deprotonation of the anilinium station, the
macrocycle shuttles toward the sole triazolium station, even
though we already reported that monosubstituted pyridinium
amide was a molecular station of very similar but slightly better
anity for the DB24C8 than the triazolium one. This result is
perfectly consistent with the fact that the benzyl moiety bonded
to the triazolium station acts also as a steric molecular barrier
that does not allow the macrocycle to pass over. This
observation was demonstrated by the comparison between
the
1
H NMR spectra of the protonated rotaxane 9 and the
deprotonated rotaxane 10 (Figure 2c,d). Unsurprisingly, in 10,
an upeld shift is observed for the hydrogen atoms H
25
, H
28
,
and H
30
(respectively, = 1.06, 1.03, and 0.61 ppm), as
a result of the deprotonation of the anilinium and the
subsequent shuttling of the DB24C8. Concomitantly, the
hydrogen atoms H
18
and H
20
belonging to the triazolium
station experience a downeld shift (respectively, = +0.90
and +1.03 ppm). By the way, it is the rst time we observed so
marked a variation of chemical shift for triazolium hydrogens
H
20
in a [2]rotaxane. We assume that the restricted
conformation adopted by the macrocycle around the triazolium
is responsible for this strong interaction by hydrogen bonding
between H
20
and the oxygen atoms of the DB24C8. This is
consistent with the presence of the bulky benzyl molecular
barrier that traps the macrocycle on only one side of the
triazolium station, more precisely around hydrogen atoms H
20
.
By comparison, it is interesting to notice that hydrogen atoms
H
20
are not involved in any hydrogen bonding interaction in
rotaxane 8, when the DB24C8 oscillates between the
monosubstituted pyridinium amide and the triazolium station.
On the contrary, in 8, it is the hydrogen atoms H
17
that interact
by hydrogen bonding with the oxygen atoms of the DB24C8.
To continue the discussion with rotaxane 10, the hydrogen
atoms H
17
and to a lesser extent H
33
and H
3537
are all more or
less shielded due to their localization in the shielding cavity of
the aromatic rings of the crown ether. No other variation in
chemical shift was noticed for the other hydrogen atoms,
especially for those of the monosubstituted pyridinium amide
station, indicating unambiguously that the DB24C8 is not
allowed to pass over the benzyl molecular barrier. The direct
comparison of the deprotonated rotaxane 10 with the
uncomplexed deprotonated thread 10u conrmed the local-
ization of the DB24C8 in 10 (Figure 2d,e), hence the molecular
machinery between 9 and 10 upon variation of pH. In brief, as
observed between the
1
H NMR spectra of rotaxanes 9 and 10,
the hydrogen atoms H
18
and H
20
of the thread 10u are shifted
downeld in the rotaxane 10 because of hydrogen bonding
interactions, whereas H
17
and to a lesser extent H
33
, H
35
, and
The Journal of Organic Chemistry Article
dx.doi.org/10.1021/jo400414f | J. Org. Chem. 2013, 78, 40994106 4102
H
37
experience an upeld shift due to their localization in the
shielding cavity of the aromatic rings of the DB24C8.

CONCLUSIONS
In conclusion, we have described two new molecular machines
incorporating a bulky side group located in the middle of the
encircled molecular axle. This bulky group acts as a kinetic
molecular barrier and allows these molecular machines to be
statistically unbalanced and away from their equilibrium in
some conditions. In the reported [2]rotaxane molecular
machines, the N-benzyltriazolium proved to serve as both a
molecular station for the DB24C8 and a molecular barrier of
sucient hindrance so that the DB24C8 cannot pass over it.
The macrocycle was trapped on either one side or the other
side of the barrier, depending on the synthetic route. Thus, two
translational isomers 8 and 9, which are not in equilibrium with
respect to each other, were synthesized and dier by the
restrained localization of the DB24C8 along the surrounded
molecular axle. The rst [2]rotaxane molecular machine 8 is
not pH-dependent: it undergoes an oscillating shuttling of its
macrocycle between the monosubstituted pyridinium amide
and the N-benzyltriazolium stations, whatever the presence of
the best anilinium station, putting this system away from its
more energetically favored co-conformation. The [2]rotaxane 9
behaves as a pH-sensitive bistable molecular machine. At the
protonated state, the DB24C8 resides around the best
anilinium station. However, deprotonation of the anilinium
triggers the shuttling of the macrocycle toward the N-
benzyltriazolium station. Here again, in 10, and similarly to
the former protonated oscillating system 8, the system remains
statistically unbalanced and not at the equilibrium due to the
kinetic molecular barrier that sterically prevents the DB24C8
from interacting with the monosubstituted pyridinium amide
station of almost comparable anity. In both molecular
machines, the interactions between the DB24C8 and the N-
benzyltriazolium station appear dierent. Restraining the
localization of a macrocycle around poorer molecular station
along a thread, out of its most energetically favored co-
conformation, could be of interest for future applications of
molecular machines.

EXPERIMENTAL SECTION
All reactions were carried out under an atmosphere of argon unless
otherwise indicated. The reagents were used as received without
further purication. Dichloromethane was distilled over P
2
O
5
and was
degassed by bubbling Ar for 20 min. Analytical thin-layer
chromatography (TLC) was performed on silica gel 60 F254 plates.
Compounds were visualized by dipping the plates in an ethanolic
solution of 10% sulphuric acid, ninhydrine, or an aqueous solution of
KMnO
4
, followed by heating.
1
H NMR and
13
C NMR spectra were
obtained respectively at 400.13 and 100.62 MHz. Chemical shifts of
1
H NMR and
13
C NMR are given in ppm by using CH
3
CN as
reference (1.94 ppm for
1
H spectrum, and 118.26 ppm for
13
C
spectrum CD
3
CN).
1
H assignments were deduced from 2D
1
H
1
H
NMR COSY experiments.
13
C assignments were deduced from 2D
13
C
1
H NMR HMQC experiments. Coupling constants (J) are
reported in hertz (Hz). Standard abbreviations indicating multiplicity
were used as follows: s (singlet), br (broad), d (doublet), t (triplet), q
(quartet), m (multiplet). Low and high-resolution ESI mass spectra
were recorded on a Q-ToF I mass spectrometer tted with an
electrospray ion source.
Starting Materials. The starting materials 1 and 2 were
synthesized according to the procedure described by Coutrot et al.
7
Synthesis and Characterizations of [2]Rotaxanes 3 and 6
10. Synthesis of Rotaxane 3. In a typical procedure, to a solution of 1
(461 mg, 0.63 mmol, 1 equiv), compound 2 (293 mg, 0.63 mmol, 1
equiv), and DB24C8 (571 mg, 1.27 mmol, 2 equiv) in dry CH
2
Cl
2
(3
mL) were successively added Cu(CH
3
CN)
4
PF
6
(238 mg, 0.63 mmol,
1 equiv) and 2,6-lutidine (7 L, 0.06 mmol, 0.1 equiv). The mixture
was stirred at rt for 24 h, and then the solvent was removed under
vacuo. The crude was directly puried by chromatography on a silica
gel column (solvent gradient elution: CH
2
Cl
2
, then 25/75 acetone/
CH
2
Cl
2
) to obtain the rotaxane 3 (783 mg, 75%) as a slightly yellow
solid. Mp 7885 C. R
f
0.62 (40/60 acetone/CH
2
Cl
2
).
1
H NMR (400
MHz, CD
3
CN, 298 K) 9.04 (d, 2H,
3
J
H7H8
= 6.9 Hz, H
7
), 8.60
8.42 (br s, 2H, H
26
), 8.35 (d, 2H,
3
J
H8H7
= 6.9 Hz, H
8
), 7.64 (br t, 1H,
H
11
), 7.41 (s, 1H, H
18
), 7.39 (t, 1H,
4
J
H30H28
=1.6 Hz, H
30
), 7.33 (d,
2H,
4
J
H28H30
= 1.6 Hz, H
28
), 6.916.80 (m, 8H, H
A
H
B
), 6.37 (d, 1H,
3
J
H1
-
H2
= 9.0 Hz, H
1
), 5.56 (t, 1H,
3
J
H3H2
=
3
J
H3H4
= 3.4 Hz, H
3
),
5.22 (dd, 1H,
3
J
H2H1
= 9.0 Hz,
3
J
H2H3
= 3.4 Hz, H
2
), 5.10 (dd, 1H,
3
J
H4H3
= 3.4 Hz,
3
J
H4H5
= 2.1 Hz, H
4
), 4.81 (dd, 1H,
3
J
H6aH6b
= 12.7
Hz,
3
J
H6aH5
= 9.2 Hz, H
6a
), 4.614.54 (m, 1H, H
5
), 4.314.25 (m,
3H, H
17
H
6b
), 4.194.05 (m, 10H, H
C
H
25
), 3.843.72 (m, 8H, H
D
),
3.653.58 (m, 4H, H
E
), 3.443.36 (m, 6H, H
E
H
12
), 2.46 (t, 2H,
3
J
H20H21
= 7.6 Hz, H
20
), 2.20 and 2.16 and 2.00 and 1.87 (4*s, 12H,
CH
3
CO), 1.861.80 (m, 2H, H
16
), 1.671.56 (m, 4H, H
13
H
24
),
1.451.27 (m, 6H, H
14
H
15
H
21
), 1.251.10 (m, 4H, H
22
H
23
), 1.18 (s,
18H, H
32
).
13
C NMR (100 MHz, CD
3
CN, 298 K) 171.5 and 170.3
and 170.0 and 169.9 (COCH
3
), 162.4 (C
10
), 153.6 (C
29
), 153.0 (C
9
),
148.4 (C
19
), 148.3 (Cq D24C8), 144.1 (C
7
), 136.1(C
27
), 127.2 (C
8
),
124.9 (C
30
), 122.1 and 113.2 (C
A
C
B
), 122.0 (C
18
), 117.8 (C
28
), 89.1
(C
1
), 78.6 (C
5
), 71.6 (C
E
), 71.0 (C
D
), 69.6 (C
2
), 69.1 (C
C
), 68.3 (C
4
),
67.4 (C
3
), 60.9 (C
6
), 51.6 (C
25
), 50.4 (C
17
), 40.9 (C
12
), 35.6 (C
31
),
31.4 (C
32
), 30.8 (C
16
), 29.9 and 29.4 and 29.4 and 28.2 and 26.7 and
26.6 and 26.4 (C
13
C
14
C
15
C
21
C
22
C
23
C
24
), 25.9 (C
20
), 21.0 and 20.9
and 20.8 and 20.4 (CH
3
CO). HRMS (ESI) [M 2PF6]
2+
calculated
for [C
72
H
104
N
6
O
18
]
2+
: 670.3704, found 670.3683
Synthesis of Rotaxane 6. To a solution of rotaxane 3 (53 mg, 0.03
mmol, 1 equiv) in CH
2
Cl
2
(2 mL) were introduced successively DIEA
(11 L, 0.06 mmol, 2 equiv) and Boc
2
O (21 mg, 0.09 mmol, 3 equiv).
The mixture was stirred at room temperature for 15 h. After solvent
evaporation, the crude was puried by chromatography on a silica gel
column (elution gradient: 5/95 acetone/CH
2
Cl
2
, then 10/90) to yield
rotaxane 6 (48 mg, 93%) as a white foam. R
f
0.43 (acetone/CH
2
Cl
2
20/80).
1
H NMR (400 MHz, CD
3
CN, 298 K) 9.31 (d, 2H,
3
J
H8H7
= 6.8 Hz, H
8
), 9.00 (d, 2H,
3
J
H7H8
= 6.8 Hz, H
7
), 7.96 (t, 1H,
3
J
H11H12
= 7.0 Hz, H
11
), 7.537.42 (br s, 1H, H
7
), 7.30 (t, 1H,
4
J
H30H28
= 1.7 Hz, H
30
), 7.03 (d, 2H,
4
J
H28H30
= 1.7 Hz, H
28
), 7.02
6.90 (m, 8H, H
A
H
B
), 6.34 (d, 1H,
3
J
H1H2
= 9.2 Hz, H
1
), 5.485.43
(t, 1H,
3
J
H3H2
=
3
J
H3H4
= 3.5 Hz, H
3
), 5.26 (dd, 1H,
3
J
H2H1
= 9.1
Hz,
3
J
H2H3
= 3.5 Hz, H
2
), 4.99 (dd, 1H,
3
J
H4H3
= 3.5 Hz,
3
J
H4H5
=
1.8 Hz, H
4
), 4.95 (dd, 1H,
2
J
H6aH6b
= 12.9 Hz,
3
J
H6aH5
= 9.7 Hz, H
6a
),
4.374.32 (m, 1H, H
5
), 4.19 (t, 2H,
3
J
H17H16
= 7.1 Hz, H
17
), 4.16
4.02 (m, 9H, H
6b
H
C
), 3.733.53 (m, 10H, H
25
H
D
), 3.203.07 (m,
10H, H
12
H
E
), 2.702.57 (m, 6H, H
20
H
E
), 2.13 and 2.00 and 1.97
and 1.84 (4*s, 12H, CH
3
CO), 1.711.63 (m, 2H, H
16
), 1.621.53 (m,
2H, H
21
), 1.511.41 (m, 2H, H
24
), 1.39 (s, 9H, H
35
), 1.29 (s, 18H,
H
32
), 1.351.26 (m, 4H, H
22
H
23
), 1.160.99 (m, 6H, H
13
H
14
H
15
).
13
C NMR (100 MHz, CD
3
CN, 298 K) 171.7 and 170.2 and 170.0
and 169.8 (COCH
3
), 163.0 (C
10
), 155.4 (C
33
), 152.4 (C
9
), 152.0
(C
29
), 148.6 (C
q DB24C8
), 143.1 (C
27
), 142.8 (C
7
), 130.1 (C
8
), 122.4
(C
28
), 122.3 (C
18
), 122.1 and 112.8 and 112.7 (C
A
C
B
), 120.6 (C
30
),
88.6 (C
1
), 80.1 (C
34
), 78.9 (C
5
), 70.3 (C
E
C
D
), 69.0 and 69.0 (C
2
C
C
),
68.1 (C
4
), 67.3 (C
3
), 60.3 (C
6
), 50.6 (C
17
C
25
), 40.6 (C
12
), 35.4 (C
31
),
31.5 (C
32
), 30.6 and 30.1 and 29.4 and 29.3 and 28.9 and 27.0 and
26.5 and 26.5 (C
13
C
14
C
15
C
16
C
21
C
22
C
23
C
24
), 28.5 (C
35
), 26.0
(C
20
), 21.0 and 20.8 and 20.8 and 20.7 (CH
3
CO). HRMS (ESI) [M
PF
6
]
+
calculated for [C
77
H
111
N
6
O
20
]
+
: 1439.7853, found 1439.7863
Synthesis of Rotaxane 7. To a solution of rotaxane 6 (40 mg, 0.025
mmol, 1 equiv) in CH
2
Cl
2
(4 mL) was introduced benzyl bromide (2
mL). After 5 days of stirring at room temperature, a solution of
NH
4
PF
6
(20 mg, 0.13 mmol, 5 equiv) in Milli-Q water (5 mL) was
added. The biphasic mixture was vigorously stirred for 30 min. After
separation, the aqueous phase was extracted with CH
2
Cl
2
(2 10
The Journal of Organic Chemistry Article
dx.doi.org/10.1021/jo400414f | J. Org. Chem. 2013, 78, 40994106 4103
mL). The organic phases were combined, dried over MgSO
4
, and
concentrated. The crude was puried by chromatography on a silica
gel column (elution gradient: 10/90 acetone/CH
2
Cl
2
, then 15/85) to
give rotaxane 7 (30 mg, 65%) as a pale yellow solid. R
f
0.50 (acetone/
CH
2
Cl
2
20/80).
1
H NMR (400 MHz, CD
3
CN, 298 K) 9.01 (d, 2H,
3
J
H7H8
= 6.9 Hz, H
7
), 8.83 (d, 2H,
3
J
H8H7
= 6.9 Hz, H
8
), 8.46 (s, 1H,
H
7
), 7.77 (t, 1H,
3
J
H11H12
= 7.0 Hz, H
11
), 7.417.37 and 7.257.21
(2*m, 5H, H
35
H
36
H
37
), 7.31 (t, 1H,
4
J
H30H28
= 1.7 Hz, H
30
), 7.02 (d,
2H,
4
J
H28H30
= 1.7 Hz, H
28
), 6.926.85 (m, 8H, H
A
H
B
), 6.35 (d, 2H,
3
J
H1H2
= 9.1 Hz, H
1
), 5.51 (t, 1H,
3
J
H3H2
=
3
J
H3H4
= 3.4 Hz, H
3
),
5.37 (s, 2H, H
33
), 5.24 (dd, 1H,
3
J
H2H1
= 9.1 Hz,
3
J
H2H3
= 3.4 Hz,
H
2
), 5.05 (dd, 1H,
3
J
H4H3
= 3.4 Hz,
3
J
H4H5
= 1.9 Hz, H
4
), 4.89 (dd,
1H,
2
J
H6aH6b
= 12.8 Hz,
3
J
H6aH5
= 9.4 Hz, H
6a
), 4.784.70 (t, 2H,
3
J
H17H16
= 7.9 Hz, H
17
), 4.484.43 (ddd, 1H,
3
J
H5H6a
= 9.4 Hz,
3
J
H5H6b
= 3.6 Hz,
3
J
H4H4
= 3.4 Hz, H
5
), 4.17 (dd, 1H,
2
J
H6bH6a
=
12.9 Hz,
3
J
H6bH5
= 3.6 Hz, H
6b
), 4.113.98 (m, 8H, H
C
), 3.723.60
(m, 8H, H
D
), 3.56 (t, 2H,
3
J
H25H24
= 7.4 Hz, H
25
), 3.323.23 (m, 4H,
H
E
), 3.213.13 (m, 2H, H
12
), 3.123.05 (m, 4H, H
E
), 2.47 (t, 2H,
3
J
H20H21
= 7.7 Hz, H
20
), 2.16 and 2.08 and 1.98 and 1.86 (4*s, 12H,
CH
3
CO), 2.051.92 (m, 2H, H
16
), 1.441.35 (m, 4H, H
21
H
24
), 1.38
(s, 9H, H
40
), 1.341.17 (m, 10H, H
13
H
14
H
15
H
22
H
23
), 1.30 (s, 18H,
H
32
).
13
C NMR (100 MHz, CD
3
CN, 298 K) 171.6 and 170.3 and
170.0 and 169.9 (COCH
3
), 162.7 (C
10
), 155.4 (C
38
), 152.6 (C
9
),
152.1 (C
29
), 148.6 (C
q DB24C8
), 143.9 (C
19
), 143.5 (C
7
), 143.0 (C
27
),
130.1 and 130.1 and 129.3 (C
35
C
36
C
37
), 129.5 (C
18
), 128.7 (C
8
),
122.3 (C
28
), 121.9 and 112.8 (C
A
C
B
), 120.7 (C
30
), 88.8 (C
1
), 80.2
(C
39
), 78.8 (C
5
), 71.0 (C
E
), 70.5 (C
D
), 69.3 (C
2
), 69.0 (C
C
), 68.2
(C
4
), 67.4 (C
3
), 60.6 (C
6
), 54.6 and 54.5 (C
17
C
33
), 50.5 (C
25
), 40.7
(C
12
), 35.4 (C
31
), 31.5 (C
32
), 29.4 and 29.0 and 28.8 and 28.3 and 27.6
and 26.8 and 26.7 and 26.3 (C
13
C
14
C
15
C
16
C
21
C
22
C
23
C
24
), 28.5
(C
40
), 23.6 (C
20
), 21.0 and 20.8 and 20.6 and 18.6 (CH
3
CO). HRMS
(ESI) [M 2PF
6
]
2+
calculated for [C
84
H
118
N
6
O
20
]
2+
: 765.4200, found
765.4195
Synthesis of Rotaxane 8. To the neat rotaxane 7 (25 mg, 0.014
mmol, 1 equiv) was added a solution of HCl 2 M in Et
2
O (4 mL).
After stirring for 1 h at room temperature, the ethereal phase was
removed, and then the crude was diluted in CH
2
Cl
2
(5 mL). A
solution of NH
4
PF
6
(11 mg, 0.068 mmol, 5 equiv) in Milli-Q water (5
mL) was introduced, and the biphasic mixture was stirred vigorously
for 30 min. After separation, the aqueous phase was extracted with
CH
2
Cl
2
(2 5 mL). The organic phases were combined, dried over
MgSO
4
, and concentrated. The crude was puried by chromatography
on a silica gel column (elution gradient: CH
2
Cl
2
, 5/95 acetone/
CH
2
Cl
2
, then 25/75) to yield rotaxane 8 as its deprotonated form.
Thus a solution of HCl 2 M in Et
2
O (4 mL) was added. After stirring
for 1 h at room temperature, the ethereal phase was removed, and the
crude was diluted in CH
2
Cl
2
(5 mL). A solution of NH
4
PF
6
(11 mg,
0.068 mmol, 5 equiv) in Milli-Q water (5 mL) was introduced, and the
biphasic mixture was stirred vigorously for 30 min. After separation,
the aqueous phase was extracted with CH
2
Cl
2
(2 5 mL). The
organic phases were combined, dried over MgSO
4
, and concentrated
to provide the protonated rotaxane 8 (15 mg, 60%) as a pale yellow
solid. R
f
0.56 (acetone/CH
2
Cl
2
30/70).
1
H NMR (400 MHz, CD
3
CN,
298 K) 9.01 (d, 2H,
3
J
H7H8
= 6.9 Hz, H
7
), 8.83 (d, 2H,
3
J
H8H7
= 6.9
Hz, H
8
), 8.47 (s, 1H, H
18
), 7.75 (t, 1H,
3
J
H11H12
= 6.8 Hz, H
11
), 7.43
7.38 and 7.277.22 (2*m, 5H, H
35
H
36
H
37
), 6.926.86 (m, 8H, H
A
H
B
), 6.84 (t, 1H,
4
J
H30H28
= 1.5 Hz, H
30
), 6.55 (d, 2H,
4
J
H28H30
= 1.5
Hz, H
28
), 6.35 (d, 1H,
3
J
H1H2
= 9.1 Hz, H
1
), 5.51 (t, 1H,
3
J
H3H2
=
3
J
H3H4
= 3.5 Hz, H
3
), 5.39 (s, 2H, H
33
), 5.25 (dd, 1H,
3
J
H2H1
= 9.1
Hz,
3
J
H2H3
= 3.5 Hz, H
2
), 5.06 (dd, 1H,
3
J
H4H3
= 3.5 Hz,
3
J
H4H5
=
1.9 Hz, H
4
), 4.89 (dd, 1H,
2
J
H6aH6b
= 12.8 Hz,
3
J
H6aH5
= 9.4 Hz, H
6a
),
4.75 (t, 2H,
3
J
H17H16
= 7.9 Hz, H
17
), 4.45 (ddd, 1H,
3
J
H5H6a
= 9.4 Hz,
3
J
H5H6b
= 3.6 Hz,
3
J
H5H4
= 1.9 Hz, H
5
), 4.17 (dd, 1H,
2
J
H6bH6a
=
12.8 Hz,
3
J
H6bH5
= 3.6 Hz, H
6b
), 4.103.99 (m, 8H, H
C
), 3.713.57
(m, 8H, H
D
), 3.323.22 (m, 4H, H
E
), 3.213.12 (m, 2H, H
12
), 3.11
3.04 (m, 6H, H
25
H
E
), 2.51 (t, 2H,
3
J
H20H21
= 7.6 Hz, H
20
), 2.16 and
2.09 and 1.98 and 1.86 (4*s, 12H, CH
3
CO), 2.061.96 (m, 2H, H
16
),
1.571.49 (m, 2H, H
24
), 1.481.38 (m, 2H, H
21
), 1.351.25 (m, 6H
H
13
H
22
H
23
), 1.27 (s, 18H, H
32
), 1.241.19 (m, 4H, H
14
H
15
).
13
C
NMR (100 MHz, CD
3
CN, 298 K) 170.2 and 170.3 and 170.0 and
169.9 (COCH
3
), 162.7 (C
10
), 152.7 (C
9
C
29
), 148.7 (C
q DB24C8
), 144.0
(C
19
), 143.5 (C
7
), 133.2 (C
34
), 130.2 and 130.2 and 129.4 (C
35
C
36
C
37
), 129.7 (C
18
), 128.8 (C
8
), 122.0 and 112.9 (C
A
C
B
), 113.5 (C
30
),
109.1 (C
28
), 88.9 (C
1
), 78.9(C
5
), 71.1 (C
E
), 70.6 (C
D
), 69.3 (C
2
), 69.1
(C
C
), 68.3 (C
4
), 67.5 (C
3
), 60.7 (C
6
), 54.6 (C
17
C
33
), 45.2 (C
25
), 40.8
(C
12
), 35.4 (C
31
), 31.7 (C
32
), 29.5 and 29.1 and 27.7 and 27.4 and 27.1
and 26.8 and 26.4 (C
13
C
14
C
15
C
21
C
22
C
23
C
24
), 28.4 (C
16
), 23.7
(C
20
), 21.0 and 20.9 and 20.6 and 20.5 (CH
3
CO). HRMS (ESI) [M
3PF
6
]
3+
calculated for [C
79
H
111
N
6
O
18
]
3+
: 477.2652, found 477.2624
Synthesis of Rotaxane 9. To a solution of rotaxane 3 (109 mg,
0.067 mmol, 1 equiv) in CH
2
Cl
2
(5 mL) was introduced benzyl
bromide (3 mL). After 4 days of stirring at room temperature, a
solution of NH
4
PF
6
(54 mg, 0.33 mmol, 5 equiv) in Milli-Q water (5
mL) was added. The biphasic mixture was stirred vigorously for 30
min at room temperature. After separation, the aqueous layer was
extracted with CH
2
Cl
2
(2 15 mL). Organic layers were combined,
dried over MgSO
4
, and then concentrated. The crude was puried by
chromatography on a silica gel column (elution gradient: 20/80
acetone/CH
2
Cl
2
, then 35/75) to yield rotaxane 9 (98 mg, 79%) as a
white foam. R
f
0.40 (acetone/CH
2
Cl
2
40/60).
1
H NMR (400 MHz,
CD
3
CN, 298 K) 9.05 (d, 2H,
3
J
H7H8
= 6.9 Hz, H
7
), 8.588.45 (br s,
2H, H
26
), 8.35 (d, 2H,
3
J
H8H7
= 6.9 Hz, H
8
), 8.06 (s, 1H, H
18
), 7.65
(t, 1H,
3
J
H11H12
= 6.9 Hz, H
11
), 7.477.39 and 7.347.28 (m, 6H,
H
30
H
35
H
36
H
37
), 7.32 (d, 2H,
4
J
H28H30
= 1.6 Hz, H
28
), 6.896.79
(m, 8H, H
A
H
B
), 6.38 (d, 1H,
3
J
H1H2
= 9.0 Hz, H
1
), 5.62 (s, 2H, H
33
),
5.57 (t, 1H,
3
J
H3H2
=
3
J
H3H4
= 3.4 Hz, H
3
), 5.22 (dd, 1H,
3
J
H2H1
=
9.0 Hz,
3
J
H2H3
= 3.4 Hz, H
2
), 5.11 (dd, 1H,
3
J
H4H2
= 3.4 Hz,
3
J
H4H5
= 2.0 Hz, H
4
), 4.82 (dd, 1H,
2
J
H6aH6b
= 12.7 Hz,
3
J
H6aH5
= 9.2 Hz,
H
6a
), 4.58 (ddd, 1H,
3
J
H5H6a
= 9.2 Hz,
3
J
H5H6b
= 3.7 Hz,
3
J
H5H4
=
2.0 Hz, H
5
), 4.53 (t, 2H,
3
J
H17H16
= 7.2 Hz, H
17
), 4.28 (dd, 1H,
2
J
H6bH6a
= 12.7 Hz,
3
J
H6bH5
= 3.7 Hz, H
6b
), 4.164.05 (m, 10H, H
25
H
C
), 3.833.72 (m, 8H, H
D
), 3.633.56 (m, 4H, H
E
), 3.433.36 (m,
6H, H
12
H
E
), 2.46 (t, 2H,
3
J
H20H21
= 7.5 Hz, H
20
), 2.21 and 2.16 and
2.00 and 1.87 (4*s, 12H, CH
3
CO), 2.001.96 (m, 2H, H
16
), 1.67
1.53 (m, 4H, H
13
H
24
), 1.481.34 (m, 4H, H
14
H
15
), 1.281.04 (m,
6H, H
21
H
22
H
23
), 1.19 (s, 18H, H
32
).
13
C NMR (100 MHz, CD
3
CN,
298 K) 171.6 and 170.3 and 170.0 and 169.9 (COCH
3
), 162.5 (C
10
),
153.7 (C
29
), 153.0 (C
9
), 148.4 (C
q DB24C8
), 145.4 (C
19
), 144.1 (C
7
),
136.1 (C
27
), 132.9 (C
34
), 130.3 and 130.2 and 129.1 (C
35
C
36
C
37
),
128.9 (C
18
), 127.2 (C
8
), 125.0 (C
30
), 122.2 and 113.3 (C
A
C
B
), 117.7
(C
28
), 89.1 (C
1
), 78.7 (C
5
), 71.6 (C
E
), 71.0 (C
D
), 69.6 (C
2
), 69.1
(C
C
), 68.3 (C
4
), 67.4 (C
3
), 60.9 (C
6
), 55.1 (C
33
), 54.7 (C
17
), 51.5
(C
25
), 40.9 (C
12
), 35.6 (C
31
), 31.4 (C
32
), 29.6 and 29.4 and 29.1 and
28.0 and 27.5 and 26.7 and 26.3 and 26.2 (C
13
C
14
C
15
C
16
C
21
C
22
C
23
C
24
), 23.7 (C
20
), 21.0 and 20.8 and 20.8 and 20.4 (CH
3
CO). HRMS
(ESI) [M 3PF
6
]
3+
calculated for [C
79
H
111
N
6
O
18
]
3+
: 477.2650, found
477.2624
Synthesis of Rotaxane 10. To a solution of rotaxane 9 in CD
3
CN
was introduced DIEA to provide the deprotonated rotaxane 10.
1
H
NMR (400 MHz, CD
3
CN, 298 K) 9.05 (d, 2H,
3
J
H7H8
= 6.9 Hz,
H
7
), 8.96 (s, 1H, H
18
), 8.33 (d, 2H,
3
J
H8H7
= 6.9 Hz, H
8
), 7.59 (t, 1H,
3
J
H11H12
= 6.9 Hz, H
11
), 7.337.18 and 7.077.02 (2*m, 5H, H
35
H
36
H
37
), 6.876.83 (m, 8H, H
A
H
B
), 6.71 (t, 1H,
4
J
H30H28
= 1.6 Hz,
H
30
), 6.40 (d, 2H,
4
J
H28H30
= 1.6 Hz, H
28
), 6.38 (d, 1H,
3
J
H1H2
= 9.1
Hz, H
1
), 5.56 (t, 1H,
3
J
H3H2
=
3
J
H3H4
= 3.5 Hz, H
3
), 5.54 (s, 2H,
H
33
), 5.22 (dd, 1H,
3
J
H2H1
= 9.1 Hz,
3
J
H2H3
= 3.5 Hz, H
2
), 5.10 (dd,
1H,
3
J
H4H3
= 3.5 Hz,
3
J
H4H5
= 2.0 Hz, H
4
), 4.81 (dd, 1H,
2
J
H6aH6b
=
12.7 Hz,
3
J
H6aH5
= 9.2 Hz, H
6a
), 4.58 (ddd, 1H,
3
J
H5H6a
= 9.2 Hz,
3
J
H5H6b
= 3.7 Hz,
3
J
H5H4
= 2.0 Hz, H
5
), 4.28 (dd,
2
J
H6bH6a
= 12.7 Hz,
3
J
H6bH5
= 3.7 Hz, H
6b
), 4.113.95 (m, 10H, H
17
H
C
), 3.803.73 (m,
4H, H
D
), 3.643.56 (m, 8H, H
E
H
D
), 3.533.45 (m, 6H, H
E
H
20
),
3.343.24 (m, 2H, H
12
), 2.94 (t, 2H,
3
J
H25H24
= 6.0 Hz, H
25
), 2.15
2.05 (m, 2H, H
21
), 2.21 and 2.16 and 2.00 and 1.87 (4*s, 12H,
CH
3
CO), 1.761.67 (m, 2H, H
16
), 1.541.43 (m, 6H, H
13
H
22
H
24
),
1.411.30 (m, 4H, H
14
H
23
), 1.24 (s, 18H, H
32
), 1.111.08 (m, 2H,
H
15
).
13
C NMR (100 MHz, CD
3
CN, 298 K) 171.6 and 170.3 and
170.0 and 169.9 (COCH
3
), 162.4 (C
10
), 152.9 (C
9
), 152.2 (C
29
),
149.1 (C
27
), 148.7 (C
q DB24C8
), 144.1 (C
7
), 130.5 (C
18
), 129.7 and
The Journal of Organic Chemistry Article
dx.doi.org/10.1021/jo400414f | J. Org. Chem. 2013, 78, 40994106 4104
129.5 and 128.9 (C
35
C
36
C
37
), 127.2 (C
8
), 121.9 and 113.3 (C
A
C
B
),
111.8 (C
30
), 107.9 (C
28
), 89.0 (C
1
), 78.6 (C
5
), 71.9 (C
E
), 70.8 (C
D
),
69.6 (C
2
), 69.5 (C
C
), 68.2 (C
4
), 67.41 (C
3
), 60.9 (C
6
), 53.9 and 53.8
(C
17
C
33
), 44.3 (C
44
), 40.8 (C
12
), 35.2 (C
31
), 31.6 (C
32
), 29.8 and 29.7
and 29.6 and 29.3 and 29.2 and 27.9 and 26.5 and 26.2 and 26.1 (C
13
C
14
C
15
C
16
C
21
C
22
C
23
C
24
), 23.7 (C
20
), 20.9 and 20.8 and 20.7 and
20.4 (CH
3
CO). HRMS (ESI) [M PF
6
]
+
calculated for
[C
79
H
110
F
6
N
6
O
18
P]
+
: 1575.7518, found 1575.7520
Synthesis and Characterizations of the Uncomplexed
Threads 7u, 9u, and 10u. Synthesis of Compound 7u. To a
solution of compound 6u
7
(112 mg, 0.098 mmol, 1 equiv) in CH
2
Cl
2
(5 mL) was introduced benzyl bromide (3 mL). After stirring for 5
days at room temperature, a solution of NH
4
PF
6
(80 mg, 0.49 mmol, 5
equiv) in Milli-Q water (5 mL) was added. The biphasic mixture was
vigorously stirred for 30 min. After separation, the aqueous phase was
extracted with CH
2
Cl
2
(2 10 mL). The organic phases were
combined, dried over MgSO
4
, and concentrated. The crude was
puried by chromatography on a silica gel column (elution gradient:
15/85 acetone/CH
2
Cl
2
, puis 35/65) to yield compound 7u (81 mg,
60%) as a colorless oil. R
f
0.43 (acetone/CH
2
Cl
2
30/70).
1
H NMR
(400 MHz, CD
3
CN, 298 K) 9.06 (d, 2H,
3
J
H7H8
= 6.9 Hz, H
7
), 8.36
(d, 2H,
3
J
H8H7
= 6.9 Hz, H
8
), 8.19 (s, 1H, H
18
), 7.66 (t, 1H,
3
J
H11H12
= 6.9 Hz, H
11
), 7.447.38 and 7.347.30 (2*m, 6H, H
30
H
35
H
36
H
37
), 7.02 (d, 2H,
4
J
H28H30
= 1.7 Hz, H
28
), 6.39 (d, 1H,
3
J
H1H2
= 9.1
Hz, H
1
), 5.65 (s, 2H, H
33
), 5.57 (t, 1H,
3
J
H3H2
=
3
J
H3H4
= 3.4 Hz,
H
3
), 5.22 (dd, 1H,
3
J
H2H1
= 9.0 Hz,
3
J
H2H3
= 3.4 Hz, H
2
), 5.10 (dd,
1H,
3
J
H4H3
= 3.4 Hz,
3
J
H4H5
= 2.0 Hz, H
4
), 4.82 (dd, 1H,
2
J
H6aH6b
=
12.7 Hz,
3
J
H6aH5
= 9.2 Hz, H
6a
), 4.59 (ddd, 1H,
3
J
H5H6a
= 9.2 Hz,
3
J
H5H6b
= 3.7 Hz,
3
J
H5H4
= 2.0 Hz, H
5
), 4.51 (t, 2H,
3
J
H17H16
= 7.2
Hz, H
17
), 4.29 (dd, 1H,
2
J
H6bH6a
= 12.8 Hz,
3
J
H6bH5
= 3.7 Hz, H
6b
),
3.57 (t, 2H,
3
J
H25H24
= 7.1 Hz, H
25
), 3.40 (q, 2H,
3
J
H12H11
=
3
J
H12H13
= 6.9 Hz, H
12
), 2.73 (t, 2H,
3
J
H20H21
= 7.7 Hz, H
20
), 2.21 and 2.17 and
2.00 and 1.88 (4*s, 12H, CH
3
CO), 2.011.93 (m, 2H, H
16
), 1.66
1.57 (m, 2H, H
13
), 1.561.47 (m, 2H, H
21
), 1.471.34 (m, 6H, H
14
H
15
H
24
), 1.38 (s, 9H, H
40
), 1.30 (s, 18H, H
32
), 1.331.20 (m, 4H, H
22
H
23
).
13
C NMR (100 MHz, CD
3
CN, 298 K) 171.5 and 170.3 and
170.0 and 169.9 (COCH
3
), 162.5 (C
10
), 155.4 (C
38
), 152.9 (C
9
),
152.1 (C
29
), 145.5 (C
19
), 144.1 (C
7
), 143.0 (C
27
), 132.9 (C
34
), 130.1
and 130.1 and 129.1 (C
18
C
35
C
36
C
37
), 127.2 (C
8
), 122.3 (C
28
), 120.7
(C
30
), 89.0 (C
1
), 80.2 (C
39
), 78.6 (C
5
), 69.6 (C
2
), 68.2 (C
4
), 67.4
(C
3
), 60.9 (C
6
), 55.1 (C
33
), 54.6 (C
17
), 50.4 (C
25
), 40.8 (C
12
), 35.4
(C
31
), 31.5 (C
32
), 29.5 and 29.2 and 28.9 and 28.5 and 27.5 and 26.6
and 26.5 and 26.0 (C
13
C
14
C
15
C
16
C
21
C
22
C
23
C
24
), 23.7 (C
20
), 20.9
and 20.8 and 20.7 and 20.4 (CH
3
CO). MS (ESI) [M 2PF
6
]
2+
calculated for [C
60
H
86
N
6
O
12
]
2+
: 541.32, found 541.31. HRMS (ESI)
[M 2PF
6
]
2+
calculated for [C
60
H
86
N
6
O
12
]
2+
: 541.3152, found
541.3192
Synthesis of Compound 8u (Equivalent to 9u). Compound 7u (25
mg, 0.018 mmol, 1 equiv) was dissolved in a solution of HCl 2 M in
Et
2
O (3 mL). After stirring for 1 h at room temperature, the ethereal
phase was removed, and then a solution of NH
4
PF
6
(15 mg, 0.09
mmol, 5 equiv) in Milli-Q water (5 mL) was introduced. After stirring
for 30 min, the precipitate was ltered and then dissolved in CH
2
Cl
2
.
The organic phase was dried over MgSO
4
and then concentrated to
yield compound 8u (15 mg, 60%) as a colorless oil.
1
H NMR (400
MHz, CD
3
CN, 298 K) 9.04 (d, 2H,
3
J
H7H8
= 6.7 Hz, H
7
), 8.36 (d,
2H,
3
J
H8H7
= 6.7 Hz, H
8
), 8.20 (s, 1H, H
18
), 7.757.69 (m, 1H, H
11
),
7.467.39 and 7.377.30 (2*m, 5H, H
35
H
36
H
37
), 6.896.84 (br s,
1H, H
30
), 6.626.57 (br s, 2H, H
28
), 6.38 (d, 1H,
3
J
H1H2
= 9.1 Hz,
H
1
), 5.66 (s, 2H, H
33
), 5.56 (t, 1H,
3
J
H3H2
=
3
J
H3H4
= 3.5 Hz, H
3
),
5.23 (dd, 1H,
3
J
H2H1
= 9.0 Hz,
3
J
H2H3
= 3.5 Hz, H
2
), 5.11 (dd, 1H,
3
J
H4H3
= 3.5 Hz,
3
J
H4H5
= 2.0 Hz, H
4
), 4.83 (dd, 1H,
2
J
H6aH6b
= 12.7
Hz,
3
J
H6aH5
= 9.2 Hz, H
6a
), 4.58 (ddd, 1H,
3
J
H5H6a
= 9.2 Hz,
3
J
H5H6b
= 3.7 Hz,
3
J
H5H4
= 2.0 Hz, H
5
), 4.50 (t, 2H,
3
J
H17H16
= 7.1 Hz, H
17
),
4.28 (dd, 1H,
2
J
H6bH6a
= 12.7 Hz,
3
J
H6bH5
= 3.7 Hz, H
6b
), 3.39 (dd,
2H,
3
J
H12H13
= 13.4 Hz,
3
J
H12H11
= 6.7 Hz, H
12
), 3.09 (t, 2H,
3
J
H25H24
= 7.1 Hz, H
25
), 2.76 (t, 2H,
3
J
H20H21
= 7.7 Hz, H
20
), 2.21
and 2.16 and 2.00 and 1.87 (4*s, 12H, CH
3
CO), 1.971.92 (m, 2H,
H
16
), 1.671.52 (m, 6H, H
13
H
21
H
24
), 1.441.25 (m, 8H, H
14
H
15
H
22
H
23
), 1.27 (s, 18H, H
32
).
13
C NMR (100 MHz, CD
3
CN, 298 K)
171.6 and 170.3 and 170.0 and 169.9 (COCH
3
), 162.5 (C
10
), 153.0
(C
9
), 152.7 (C
29
), 150.0 (C
27
), 145.6 (C
19
), 144.2 (C
7
), 133.0 (C
34
),
130.3 and 130.2 and 129.6 and 129.2 (C
18
C
35
C
36
C
37
), 127.3 (C
8
),
113.2 (C
30
), 109.6 (C
28
), 89.1 (C
1
), 78.7 (C
5
), 69.6 (C
2
), 68.2 (C
4
),
67.5 (C
3
), 60.9 (C
6
), 55.2 (C
33
), 54.7 (C
17
), 45.3 (C
25
), 40.9 (C
12
),
35.4 (C
31
), 31.6 (C
32
), 29.6 and 29.5 and 29.4 and 28.9 and 27.6 and
27.0 and 26.7 and 26.1 (C
13
C
14
C
15
C
16
C
21
C
22
C
23
C
24
), 23.6 (C
20
),
21.0 and 20.9 and 20.8 and 20.5 (CH
3
CO). MS (ESI) [M 3PF
6
]
3+
calculated for [C
55
H
79
N
6
O
10
]
3+
: 327.86, found 328.08. HRMS (ESI)
[M PF
6
]
+
calculated for [C
55
H
79
N
6
O
10
F
12
P
2
]
+
: 1273.5141, found
1273.5115
Synthesis of Compound 10u. To a solution of 8u in CD
3
CN was
added DIEA to provide compound 10u.
1
H NMR (400 MHz,
CD
3
CN, 298 K) 9.04 (d, 2H,
3
J
H7H8
= 6.9 Hz, H
7
), 8.36 (d, 2H,
3
J
H8H7
= 6.9 Hz, H
8
), 8.18 (s, 1H, H
18
), 7.72 (t, 1H,
3
J
H11H12
= 7.0
Hz, H
11
), 7.457.40 and 7.357.31 (2*m, 5H, H
35
H
36
H
37
), 6.73 (t,
1H,
4
J
H30H28
= 1.7 Hz, H
30
), 6.45 (d, 2H,
4
J
H28H30
= 1.7 Hz, H
28
),
6.38 (d, 1H,
3
J
H1H2
= 9.0 Hz, H
1
), 5.66 (s, 2H, H
33
), 5.56 (t, 1H,
3
J
H3H2
=
3
J
H3H4
= 3.4 Hz, H
3
), 5.23 (dd, 1H,
3
J
H2H1
= 9.0 Hz,
3
J
H2H3
= 3.4 Hz, H
2
), 5.11 (dd, 1H,
3
J
H4H3
= 3.4 Hz,
3
J
H4H5
= 2.0
Hz, H
4
), 4.83 (dd, 1H,
2
J
H6aH6b
= 12.8 Hz,
3
J
H6aH5
= 9.2 Hz, H
6a
),
4.58 (ddd, 1H,
3
J
H5H6a
= 9.2 Hz,
3
J
H5H6b
= 3.7 Hz,
3
J
H5H4
= 2.0 Hz,
H
5
), 4.50 (t, 2H,
3
J
H17H16
= 7.2 Hz, H
17
), 4.28 (dd, 1H,
2
J
H6bH6a
=
12.8 Hz,
3
J
H6bH5
= 3.7 Hz, H
6b
), 3.39 (dd, 2H,
3
J
H12H13
= 13.0 Hz,
3
J
H12H11
= 7.0 Hz, H
12
), 3.05 (t, 2H,
3
J
H25H24
= 7.0 Hz, H
25
), 2.76 (t,
2H,
3
J
H20H21
= 7.5 Hz, H
20
), 2.21 and 2.17 and 2.00 and 1.88 (4*s,
12H, CH
3
CO), 1.991.90 (m, 2H, H
16
), 1.651.48 (m, 6H, H
13
H
21
H
24
), 1.451.32 (m, 8H, H
14
H
15
H
22
H
23
), 1.26 (s, 18H, H
32
).
13
C
NMR (100 MHz, CD
3
CN, 298 K) 170.3 and 170.1 and 170.0 and
169.9 (COCH
3
), 162.5 (C
10
), 153.0 (C
9
), 152.4 (C
29
), 149.6 (C
27
),
145.6 (C
19
), 144.2 (C
7
), 133.0 (C
34
), 130.3 and 130.2 and 129.2 (C
18
C
35
C
36
C
37
), 127.3 (C
8
), 112.0 (C
30
), 108.0 (C
28
), 89.1 (C
1
), 78.7
(C
5
), 69.6 (C
2
), 68.3 (C
4
), 67.5 (C
3
), 61.0 (C
6
), 55.2 (C
33
), 54.7
(C
17
), 44.3 (C
25
), 40.9 (C
12
), 35.3 (C
31
), 31.6 (C
32
), 29.8 and 29.5 and
29.4 and 29.1 and 27.7 and 27.2 and 26.7 and 26.1 (C
13
C
14
C
15
C
16
C
21
C
22
C
23
C
24
), 23.8 (C
20
), 21.0 and 20.9 and 20.8 and 20.5
(CH
3
CO). MS (ESI) [M 2PF
6
]
2+
calculated for [C
55
H
78
N
6
O
10
]
2+
:
491.29, found 491.28. HRMS (ESI) [M PF
6
]
+
calculated for
[C
55
H
78
N
6
O
10
F
6
P]
+
: 1127.5414, found 1127.5421

ASSOCIATED CONTENT
*S Supporting Information
All NMR spectra of rotaxanes and uncomplexed threads. This
material is available free of charge via the Internet at http://
pubs.acs.org.

AUTHOR INFORMATION
Corresponding Author
*E-mail: frederic.coutrot@univ-montp2.fr.
Notes
The authors declare no competing nancial interest.

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